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Comparison of the Sensitivities of Human, Canine, and Murine Hematopoietic Precursor Cells to Adriamycin and N-Trifluoroacetyladriamycin-14-valerate¹

Departments of Medicine and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

The sensitivities of leukocyte-committed stem cells of human, dog, and mouse bone marrow to an 18-hr exposure to Adriamycin (ADR) and N-trifluoroacetyladriamycin-14-valerate (AD32) were compared using the agar diffusion chamber assay. The survival of in situ mouse marrow stem cells following the drugs was also measured. The in vivo doses required to produce 37% survival of hematopoietic precursor cells for human, dog, mouse, and in situ mouse marrow stem cells for ADR were 9.5, 3.5, 8, and 8 mg/kg, respectively, while those for AD32 were 22, 17, 37, and 40 mg/kg. Mouse bone marrow cellularity was reduced to 50% by drug doses producing 3 and 7% stem cell survival.

AD32 given i.p. to mice was less effective than i.v. drug in producing marrow stem cell death, reduction of marrow cellularity, or acute lethality.

Although more AD32 than ADR was required to kill marrow stem cells from each species and canine marrow stem cells were the most sensitive to either drug, human stem cells were relatively more sensitive to AD32 than were mouse stem cells. The reverse was true for ADR. Granulocytopenia may be an important limiting toxicity in the clinical use of AD32.

¹ Supported by Grant CH-37 from the American Cancer Society and Grants CA 18341 and CA 08341 from the National Cancer Institute.

Received 7/27/78. Accepted 10/20/78.